Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a multicentre trial, 82 patients known to be hepatitis B e antigen and hepatitis B virus DNA positive for at least 1 year, with elevated serum alanine aminotransferase levels and chronic liver lesions on biopsy, were randomized to receive either recombinant interferon alfa-2a at a dose of 4.5 million units thrice weekly for 4 months or no treatment. At the end of therapy, viral DNA clearance and aminotransferase normalization were significantly (p less than 0.05) more frequent in treated patients than in controls. After 16 months' follow up, the difference was still significant for hepatitis B e antigen clearance and transaminase normalization. Hepatitis B virus DNA reactivation was observed during follow up in 43% of treated patients and 50% of controls. Improvements in liver inflammation were observed in patients on interferon. High pre-treatment serum aminotransferase levels, female sex and a low score for fibrosis in the initial biopsy were predictive factors significantly (p less than 0.05) associated with termination of hepatitis B virus replication in treated cases. These results indicate that interferon is effective in inducing clearance of HBV from serum and improvement of biochemical and histological parameters of liver disease. However, a more prolonged regimen of therapy may be required to obtain stable suppression of hepatitis B virus replication.
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PMID:Problems in the management of chronic hepatitis B with interferon: experience in a randomized, multicentre study. 207 70

A randomized controlled trial of recombinant interferon alfa-2b has been initiated in patients with chronic active hepatitis who were negative for serum hepatitis B e antigen but positive for serum hepatitis B virus DNA and hepatitis B core antigen expression in the liver. Twenty-five patients received interferon alfa-2b 3 million units thrice weekly for 14-16 weeks and 25 served as untreated controls. Seventeen patients in the treatment and 18 in the control group have already completed a 12-month period of observation. Interferon alfa-2b was well tolerated by all patients. At the end of therapy, complete responses, defined as disappearance of hepatitis B virus DNA from serum and return of alanine aminotransferase to normal, were observed in 10 (59%) of the 17 treated patients compared to none in the control group (p less than 0.01). Twelve months after the onset of interferon alfa-2b therapy, 11 (65%) of the 17 treated patients were complete responders compared to 2 (11%) of 18 in the control group (p less than 0.01). Fifty per cent (4/8) of complete responders to interferon alfa-2b therapy, followed for 16-24 months, experienced reactivations of hepatitis B virus replication with reappearance of serum hepatitis B virus DNA and a return of serum alanine aminotransferase activity. The response to interferon alfa-2b therapy appeared to be independent of pre-treatment serum alanine aminotransferase and hepatitis B virus DNA levels.
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PMID:Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B. 207 71

Liver biopsies from 52 patients with chronic hepatitis B were investigated for the presence and distribution of HBcAg and the results were compared with the status of hepatitis B virus deoxyribonucleic acid (HBV-DNA). The patients consisted of 37 men and 15 women, aged 16-55 years (mean = 34 years). Serum alanine aminotransferase (ALT) was elevated in 50 patients (range: 18-969 U/L; mean = 290 U/L). Serological testing showed HBsAg in all, HBeAg in 45 (87%), and HBV-DNA in 28 (54%). Liver biopsies demonstrated HBcAg in 35 (67%) patients. HBcAg was not only present in 31 of 45 (69%) patients who were seropositive for HBeAg, but also in four of seven (57%) with antibody to HBeAg (anti-HBe). In 28 of 35 (80%) patients with HBcAg in the liver, serum HBV-DNA was detected. However, no serum HBV-DNA was detected in 17 patients who had no detectable HBcAg in the liver. The distribution of HBcAg in the liver was rather cytoplasmic and nuclear than nuclear alone. Among 33 patients with cytoplasmic HBcAg in the liver, 15 (45%) had an evidence of acute exacerbation of hepatitis with marked ALT elevation (range: 168-894 U/L; mean = 385 U/L) and nine patients showed severe chronic active hepatitis and confluent necrosis, histologically. These results indicate that the presence of HBcAg in the liver correlates with the amount of circulating hepatitis B virus as quantified by serum level of HBV-DNA. The predominant cytoplasmic HBcAg in the liver may suggest the possibility of multiple episodes of acute exacerbation and more severe ongoing hepatitis during the clinical course.
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PMID:Significance of hepatitis B core antigen in the liver in patients with chronic hepatitis B and its relation to hepatitis B virus DNA. 210 4

In order to assess the sequential changes of liver pathology after interferon therapy, 70 liver biopsy specimens, collected from 23 HBeAg-positive patients with chronic hepatitis B and 12 patients with chronic non-A, non-B hepatitis, were studied using a numerical scoring system proposed by Knodell et al. The biopsy specimens were obtained immediately prior to the administration of interferon and within one week following the termination of interferon therapy. Three patients with chronic hepatitis B were negative for DNA-polymerase (DNA-P) prior to the interferon administration. Ten patients (50%) lost DNA-P activity. HBeAg became negative in 8 patients (34.8%), of whom 2 seroconverted to anti-HBe. Serum alanine aminotransferase levels normalized in 9 patients with chronic hepatitis B, and non-A, non-B hepatitis. The total Histological Activity Index (HAI) scores in both patients with chronic hepatitis B, and non-A, non-B decreased significantly (P less than 0.001 and P less than 0.005, respectively) after interferon treatment. There was also a significant improvement (0.02 less than P less than 0.001) in each histological category except for fibrosis. When the changes of the HAI scores in patients with chronic hepatitis B were correlated to the outcome in the DNA-P and HBeAg/anti-HBe system after treatment, the histological improvement did not significantly correlate to the outcome of these serological parameters.
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PMID:Histological improvement of chronic hepatitis B, and non-A, non-B with interferon treatment: application of a numerical scoring system for evaluating sequential morphologic changes. 210 67

Pharmacokinetics, tolerance and biological effects of human recombinant gamma-interferon were studied in 12 patients with chronic active hepatitis B. Serum concentrations of gamma-interferon were measured by radioimmunoassay in four patients after a subcutaneous injection of 10 million U (0.5 mg); the peak serum concentration of gamma-interferon (29 +/- 7 U/ml) was reached after 5 to 8 hr and gamma-interferon remained detectable for 24 to 36 hr. Twelve patients received recombinant gamma-interferon, 2.5 to 10 million U daily, for 4 mo. All suffered from a dose-dependent, flulike syndrome similar to that induced by alpha-interferon. Recombinant gamma-interferon induced a marked increase of serum ALT and a significant decrease of serum hepatitis B virus-DNA. Serum hepatitis B virus-DNA disappeared in one patient during administration of recombinant gamma-interferon. Serum hepatitis B virus-DNA disappeared in four additional patients, and HBeAg disappeared in two patients during the 12 mo after administration of recombinant gamma-interferon. These results indicate that subcutaneous injection is suitable for administration of recombinant gamma-interferon and that recombinant gamma-interferon has an antiviral effect in patients with chronic active hepatitis B.
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PMID:Recombinant human gamma-interferon in patients with chronic active hepatitis B: pharmacokinetics, tolerance and biological effects. 211 94

Serum DNA polymerase activity (DNA-P) was detected in 27.6 per cent of non-A, non-B (NANB) hepatitis patients, 8.7 per cent of patients with alcoholic liver disease (ALD), 8.6 per cent of hepatitis B surface antigen (HBsAg)-positive patients and 19.0 per cent of HBsAg-negative blood donors with elevated serum glutamic-pyruvic transaminase (SGPT) concentrations. In contrast, none of the patients with hepatitis A, drug-induced liver injury or non-alcoholic fatty liver had DNA-P in their sera in the acute phase of the illness. All HBsAg-positive samples with detectable DNA-P were strongly positive for hepatitis B virus (HBV) DNA, but the samples from patients with NANB hepatitis and ALD and HBsAg-negative blood donors had no HBV DNA. Sensitivity to actinomycin D showed the heterogeneity of DNA-Ps in HBsAg-negative blood donors; the enzyme activity of one type was inhibited by 100 micrograms/ml of actinomycin D, whereas the other was not. The preference for exogenous template primers of these DNA-Ps was different to those of HBV and human retroviruses. The results reveal the prevalence of serum DNA-P in NANB hepatitis patients and suggest that two distinct agents are relevant to the aetiology of NANB hepatitis.
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PMID:Prevalence and heterogeneity of serum DNA polymerase activity in patients with non-A, non-B hepatitis and HBsAg-negative blood donors with elevated SGPT. 212 73

Polypeptides encoded by the pre-S1 and pre-S2 genes of hepatitis B virus (HBV) (pre-S1 antigen and pre-S2 antigen) were detected by enzyme-linked immunosorbent assay (ELISA) in 137 serum samples of patients with HBV infection. The HBV-DNA level closely correlated with the titer of pre-S antigens. However, HBV-DNA levels more closely correlated with the titer of the pre-S1 antigen [HBV-asymptomatic carrier (ASC): n = 40, r = 0.800, P less than 0.01; chronic hepatitis B (CH): n = 60, r = 0.730, P less than 0.01] than with the titer of the pre-S2 antigen [ASC: r = 0.675, P less than 0.01; CH: r = 0.575, P less than 0.01]. Thirty patients with CH, in whom hepatitis e antigen (HBeAg) was cleared after acute exacerbation (AE) [alanine aminotransferase (ALT) level greater than 200 IU/L] and the ALT level normalized, were followed for 12 months and classified into two groups: Group 1, those in whom HBeAg reappeared with an elevated ALT level within 12 months, and Group 2, those in whom HBeAg was persistently cleared from the serum and a normal ALT level continued. Of the 30 patients, 24 (80%) were classified into Group 1 and 6 (20%) were classified into Group 2. Changes in serum levels of HBV markers a month before and after AE were observed. The HBV-DNA level and DNA-P activity became negative after AE in both groups. The titer of pre-S1 antigen also decreased after AE, and no significant differences were observed between Group 1 and Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes of pre-S1 and pre-S2 antigens in sera of patients with hepatitis B virus infection. 217 Feb 20

The molecular mechanisms of reversion in mammalian cells were studied utilizing the pZipGptNeo shuttle vector, with the bacterial gpt gene in the vector integrated into the chromosomal DNA of mouse cells. From mutant cell lines containing gpt genes with single base changes, revertants were selected for the reappearance of GPT activity. The copy number and expression of the gpt genes in such revertants were analyzed, and the GPT activity encoded by revertant genes in both mammalian cells and bacteria characterized. Revertants with wild-type amino acid sequence had, on average, the highest levels of GPT activity. Revertants with amino acid sequences different from the original mutants but not corresponding to wild-type had, on average, approximately half the level of GPT activity as wild-type revertants. Revertants that still contained the original mutation in the gpt gene had even lower levels of activity. These revertants were found to have amplified mutant gpt genes, which, when transferred into bacteria, were seen to encode for GPT polypeptides with partial enzymatic activity. A revertant in which the original mutation that destroyed the AUG translational start codon was retained but in which there was a secondary mutation upstream of the start codon also was characterized. The second mutation generated an in-frame CUG codon that apparently functioned as an alternative, upstream translational start codon.
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PMID:Analysis of GPT activity in mammalian cells with a chromosomally integrated shuttle vector containing altered gpt genes. 218 99

During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children. 221 Jun 69

Markers of hepatitis B virus (HBV) and immune response against them were studied in 18 chronic asymptomatic carriers, 8 patients of the virus induced chronic liver disease (CLD), and 7 patients of chronic alcoholic liver cirrhosis, who were also chronic HBV carriers (CALC). The LMI responses to HBeAg were elevated in HBeAg and/or HBV-DNA positive chronic asymptomatic carriers, (median response 31.5%), along with elevation of serum alanine aminotransferase (sALT) levels (59-150 IU/l). On the other hand the LMI responses to this antigen, in HBeAg and HBV-DNA negative chronic carriers were in the normal range (median response 12%) and their sALT levels were also normal (7-50 IU/l). The CLD and CALC patients did not show any relation between their LMI to HBeAg and sALT levels. In contrast no relation between LMI to HBsAg and sALT levels was observed in any group. The LMI responses to HBsAg in CLD patients were elevated (median response 38%) and the responses of chronic asymptomatic carriers and CALC patients were either in the normal range or poor (median responses, 18 and 7% respectively), irrespective of their sALT levels. These results suggest that T cell responses to both the antigens may be involved in liver cell damage.
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PMID:Immune response to hepatitis B viral antigens in chronic infection & its relationship with liver necrosis. 222 52


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